A first-in-human clinical trial of ultrasmall inorganic hybrid nanoparticles, “C dots” (Cornell dots), in patients with metastatic melanoma is described for the imaging of cancer. These renally excreted silica particles were labeled with 124I for positron emission tomography (PET) imaging and modified with cRGDY peptides for molecular targeting. 124I-cRGDY–PEG–C dot particles are inherently fluorescent, containing the dye, Cy5, so they may be used as hybrid PET-optical imaging agents for lesion detection, cancer staging, and treatment management in humans. However, the clinical translation of nanoparticle probes, including quantum dots, has not kept pace with the accelerated growth in minimally invasive surgical tools that rely on optical imaging agents. The safety, pharmacokinetics, clearance properties, and radiation dosimetry of 124I-cRGDY–PEG–C dots were assessed by serial PET and computerized tomography after intravenous administration in patients. Metabolic profiles and laboratory tests of blood and urine specimens, obtained before and after particle injection, were monitored over a 2-week interval. Findings are consistent with a well-tolerated inorganic particle tracer exhibiting in vivo stability and distinct, reproducible pharmacokinetic signatures defined by renal excretion. No toxic or adverse events attributable to the particles were observed. Coupled with preferential uptake and localization of the probe at sites of disease, these first-in-human results suggest safe use of these particles in human cancer diagnostics.

FDG-PET scanning is a simple, expensive, but powerful means to restage thyroid cancer patients who develop subsequent metastases, assigning them to groups that are either at low (FDG negative) or high (FDG positive) risk of cancer-associated mortality. We propose that the aggressiveness of therapy for metastases should match the FDG-PET status.

As for other solid tumors, malignant cutaneous melanoma drains in a logical way through the lymphatic system, from the first to subsequent levels. Therefore, the first lymph node encountered (the sentinel node) will most likely be the first to be affected by metastasis, and a negative sentinel node makes it highly unlikely that other nodes in the same lymphatic basin are affected. Sentinel lymph node biopsy distinguishes patients without nodal metastases, who can avoid nodal basin dissection with its associated risk of lymphedema, and those with metastatic involvement who might benefit from additional therapy. This procedure represents a significant advantage as a minimally invasive procedure, considering that only an average 20% of melanoma patients with Breslow thickness between 1.5 and 4 mm harbour metastasis in their sentinel node(s) and are therefore candidates to elective lymph node dissection procedures. The cells that originate cutaneous melanomas are located between dermis and epidermis, a zone that drains to the inner lymphatic network in the reticular dermis, in turn to larger collecting lymphatics in subcutis. Therefore, the optimal modality of interstitial administration of radiocolloids for lymphoscintigraphy and subsequent radioguided sentinel lymph node biopsy is through intradermal/subdermal injection. (99m)Tc-labeled colloids in various size ranges are equally adequate for radioguided sentinel lymph node biopsy in patients with cutaneous melanoma, depending on local experience and availability. For melanomas located in the midline area of the head, neck, and trunk, particular consideration should be given to ambiguous lymphatic drainage, which frequently requires interstitial administration virtually all around the tumor or surgical scar from prior excision of the melanoma. Lymphoscintigraphy is an essential part of radioguided sentinel lymph node biopsy because images are used to direct the surgeon to the sites of the node(s). The sentinel lymph node should have a significantly higher count than that of background (at least 10:1 intraoperatively). After removal of the sentinel node, the surgical bed must be reexamined to ensure that all radioactive sites are identified and removed for analysis. The success rate of radioguidance in localizing the sentinel lymph node in melanoma patients is about 98% in institutions where a high number of procedures are performed, approaching 99% when combined with the vital blue dye technique. The procedure is becoming the standard of care for patients with cutaneous melanoma because of its high prognostic value that has led to include the procedure in the most recent version of the TNM staging system.

The objective of this study was to determine whether posttherapy 131 I SPECT/CT changed the need for additional crosssectional imaging or modified the American Thyroid Association risk of recurrence classification. We performed planar imaging and SPECT/CT in a consecutive series of patients after 131 I therapy. Methods: Planar imaging and SPECT/CT were performed on 148 consecutive patients with thyroid carcinoma (125 papillary, 2 follicular, 8 Hü rthle cell, and 13 poorly differentiated) approximately 5 d after the therapeutic administration of 1,739-8,066 MBq (47-218 mCi) of 131 I. The indication for treatment was postsurgical ablation (n 5 109) or recurrent or metastatic disease with rising thyroglobulin levels (n 5 39). SPECT/CT scans were obtained for all subjects for 1 bed position (38 cm), which included the neck and upper chest. Additional SPECT/CT scans of the abdomen or pelvis were acquired if suggestive findings were noted on planar images. All patients were treated in real time, according to the standard of care in our practice. At that time, clinical decisions regarding thyroid tumor classification were made by our multidisciplinary group based on all data, including operative findings, pathology, imaging, and thyroglobulin levels. In a retrospective analysis, planar and SPECT/CT images were interpreted independently, and sites of uptake were categorized as likely benign, malignant, or equivocal. An experienced thyroid endocrinologist used a combination of surgical histopathology and scan findings to determine whether additional cross-sectional imaging was required and determined if the imaging findings changed the patient's risk category. Results: In 29 patients, 61 additional cross-sectional imaging studies were avoided using SPECT/ CT, compared with medical decision making based on the planar images alone. In 7 of 109 postsurgical patients, SPECT/CT findings changed the initial American Thyroid Association risk of recurrence classification. The sensitivity of planar imaging and SPECT/CT for identification of focal 131 I uptake in the thyroid bed was similar in the postsurgical and recurrence cohorts. For metastatic disease in the neck, characterization of 131 I uptake by SPECT/CT in the postsurgical group was significantly better than that by planar scanning (P , 0.01). Among the 109 postsurgical patients, the characterization of iodine uptake in the lung, liver, and bone was also more accurate using SPECT/ CT than planar scanning (P , 0.01). The CT portion of SPECT/CT demonstrated non-iodine-avid lesions in 32 of 148 patients. Conclusion: SPECT/CT data provided information that reduced the need for additional cross-sectional imaging in 29 patients (20%) and significantly altered the initial risk of recurrence estimates in 7 of 109 patients (6.4%), thereby altering patient management recommendations with regard to frequency and intensity of follow-up studies.